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A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice

Choi, Ko‐Eun ; Hall, Casey L. ; Sun, Jin‐Mei ; Wei, Ling ; Mohamad, Osama ; Dix, Thomas A. ; Yu, Shan P.

The FASEB journal, 2012-07, Vol.26 (7), p.2799-2810 [Periódico revisado por pares]

United States: Federation of American Societies for Experimental Biology

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Título:
A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice
Autor: Choi, Ko‐Eun ; Hall, Casey L. ; Sun, Jin‐Mei ; Wei, Ling ; Mohamad, Osama ; Dix, Thomas A. ; Yu, Shan P.
Assuntos: Animals ; Apoptosis - drug effects ; autophagy ; Autophagy - drug effects ; Body Temperature - drug effects ; Brain Ischemia - complications ; Brain Ischemia - pathology ; Brain Ischemia - physiopathology ; Brain Ischemia - therapy ; brain protection ; Cerebral Infarction - pathology ; Cerebral Infarction - physiopathology ; Cerebral Infarction - prevention & control ; Cerebral Infarction - therapy ; Cerebrovascular Circulation - drug effects ; Disease Models, Animal ; Hypothermia, Induced - methods ; Male ; Mice ; Mice, Inbred C57BL ; Motor Skills - drug effects ; Neuroprotective Agents - administration & dosage ; Neuroprotective Agents - chemistry ; Neurotensin - administration & dosage ; Neurotensin - analogs & derivatives ; Neurotensin - chemistry ; neurotensin analog ; Oligopeptides - administration & dosage ; Oligopeptides - chemistry ; Receptors, Neurotensin - agonists ; Research Communications ; sensorimotor function
É parte de: The FASEB journal, 2012-07, Vol.26 (7), p.2799-2810
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SourceType-Scholarly Journals-1
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Descrição: ABSTRACT Compelling evidence from preclinical and clinical studies has shown that mild to moderate hypothermia is neuroprotective against ischemic stroke. Clinical applications of hypothermia therapy, however, have been hindered by current methods of physical cooling, which is generally inefficient and impractical in clinical situations. In this report, we demonstrate the potential of pharmacologically induced hypothermia (PIH) by the novel neurotensin receptor 1 (NTR1) agonist ABS‐201 in a focal ischemic model of adult mice. ABS‐201 (1.5‐2.5 mg/kg, i.p.) reduces body and brain temperature by 2–5°C in 15–30 min in a dose‐dependent manner without causing shivering or altering physiological parameters. Infarct volumes at 24 h after stroke are reduced by ∼30‐40% when PIH therapy is initiated either immediately after stroke induction or after 30–60 min delay. ABS‐201 treatment increases bcl‐2 expression, decreases caspase‐3 activation, and TUNEL‐positive cells in the peri‐infarct region, and suppresses autophagic cell death compared to stroke controls. The PIH therapy using ABS‐201 improves recovery of sensorimotor function as tested 21 d after stroke. These results suggest that PIH induced by neurotensin analogs represented by ABS‐201 are promising candidates for treatment of ischemic stroke and possibly for other ischemic or traumatic injuries.Choi, K.‐E., Hall, C. L., Sun, J.‐M., Wei, L., Mohamad, O., Dix, T. A., Yu, S. P. A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice. FASEB J. 26, 2799–2810 (2012). www.fasebj.org
Editor: United States: Federation of American Societies for Experimental Biology
Idioma: Inglês

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A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice

Choi, Ko‐Eun ; Hall, Casey L. ; Sun, Jin‐Mei ; Wei, Ling ; Mohamad, Osama ; Dix, Thomas A. ; Yu, Shan P.

United States: Federation of American Societies for Experimental Biology

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